The use of radioactive decay to treat cancer has been a widely used method in cancer treatment since its discovery. However, many such treatment methods involve the irradiation of the general area of the cancer, thus potentially causing harm to healthy tissues in the process. Targeted therapy is an emerging field of research where therapeutic radioisotopes are delivered directly to the cancer cells of interest by attaching them to a targeting moiety (ligand, small molecule, or protein) that has a high affinity for the cancer cells being targeted. Targeted alpha therapy (TAT) is the use of isotopes that decay by emitting α-particles, and is of particular interest because α-emission is associated with a high linear energy transfer (LET), meaning suitable emitters can deliver a large radiation dose to tissue within a short range (about 100 μm). Thus, the majority of the damage occurs within the cancer cells with a minimal impact to the surrounding healthy tissue.
Thorium-226 (226Th) is an isotope of interest for targeted alpha therapy. It has a half-life of 30.6 minutes and decays via a four alpha decay chain to long-lived lead-210 (210Pb), which has a half-life of 22.3 years. Thorium-226 emits a 111 keV gamma-ray (3.29%) that can be used for single-photon emission computed tomography (SPECT) imaging, thus providing theranostic capabilities. Due to the relatively short half-life of 226Th, a generator is useful to provide a consistent supply of this isotope from its parent uranium-230 (230U), which has a half-life of 20.23 days.
Several separation strategies have been researched and developed for the separation of uranium and thorium. These separation methods involve the use of solvent extraction, solid phase extraction, and anion exchange chromatography. However, these approaches include the use of strong acids that would denature any peptides or proteins that were labeled with the 226Th. Consequently, the 226Th eluent has to be treated (via evaporation or pH adjustment) prior to being suitable for chelation reactions. The amount of time lost in this process, which typically requires at least one 226Th half-life of radiochemical operation (i.e. about 30 minutes), is disadvantageous for providing high radiochemical yields.